TaoMedAI/RareMedData huggingface dataset:
Punctate palmoplantar keratoderma type 1 (ORPHA:79501)
A rare hereditary skin disease characterized by irregularly distributed epidermal papular/punctate hyperkeratosis of the palms and soles with wide variation among patients.
Epidemiology
The prevalence of PPKP1 has been estimated at 1.17/100,000 in Croatia and 3.3/100,000 in Slovenia. PPKP1 has been reported in over 400 patients worldwide to date.
Clinical description
Typical clinical characteristics are multiple hyperkeratotic papules and central indentations that are irregularly distributed on the palms and soles. The lesions usually start to develop in early adolescence but can also present earlier or later in life. Sometimes additional confluent thickening of the soles can be observed. Depending on the clinical presentation, PPKP1 can be associated with pain at pressure points, especially on the soles. The lesions may coalesce over pressure points. There can be considerable variation between affected family members.
Etiology
Mutations in the AAGAB gene (15q22.33-q23) have been identified as one of the causes of PPKP1. This gene encodes for the alpha and gamma-adaptin-binding protein p34 which is involved in the clathrin-mediated pathway and when disrupted causes an increase in the half-life of several receptor tyrosine kinases in basal keratinocytes, leading to hyperproliferation and hyperkeratosis. COL14A1 (8q24.12) is another gene that has been suggested to be implicated in the pathogenesis of PPKP1, but this association needs further confirmation, as it has only been reported once in a few cases from the same Chinese family.
Diagnostic methods
Mutational analysis of the AAGAB gene and the COL14A1 gene confirms the clinical diagnosis. Although not specific for PPKP1, histological examination of papules reveals hypergranulosis and hyperkeratosis with a well-defined central epidermal depression.
Differential diagnosis
Differential diagnosis includes verrucae vulgaris and any other form of palmoplantar keratoderma, primarily the focal types, such as porokeratosis punctata palmaris et plantaris (PPKP2) and focal acral hyperkeratosis (or PPKP3 without elastoidosis).
Genetic counseling
PPKP1 is inherited in an autosomal-dominant manner. Genetic counseling is possible.
Management and treatment
Mechanical removal of the hyperkeratosis is the most effective symptomatic treatment. Keratolytic creams can support the treatment. In some patients with a severe phenotype, oral retinoids have been shown to reduce symptoms.
Prognosis
Although the clinical appearance of lesions can worsen over time, the general prognosis is good. Depending on the clinical severity and pain sensitivity of patients, quality of life can be affected.

                            Last update: 
                            December 2022


                            - Expert reviewer(s): 
                            Dr M.C. [Marieke] BOLLING | ERN-Skin* - Dr P.C. [Peter] VAN DEN AKKER | ERN-Skin*


                                * European Reference Network
Punctate palmoplantar keratoderma type 2 (ORPHA:79502)
Punctate palmoplantar keratoderma type 2 is a type of isolated, punctate, hereditary palmoplantar keratoderma characterized by multiple, asymptomatic, 1 to 2 mm-long, firm, hyperkeratotic projections ('spiny keratosis') on the palms, soles and digits (typically confined to their volar and/or lateral aspects). Histopathologically, compact columnar parakeratosis over hypo- or agranular epidermis is observed.
PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (ORPHA:438213)
A rare neurologic disease characterized by neonatal hypotonia, global developmental delay, feeding difficulties, and often seizures or seizure-like episodes. Other frequently observed signs and symptoms include variable dysmorphic features, myopathic facies, respiratory problems, and visual abnormalities, such as strabismus or esotropia. Brain imaging may show delayed myelination and other white matter abnormalities.
Pure hair and nail ectodermal dysplasia (ORPHA:69084)
Pure hair and nail ectodermal dysplasia is characterised by the association of onychodystrophy and severe hypotrichosis, which is mainly limited to the scalp but may also affect the eyelashes and eyebrows. Less than 20 cases have been reported so far. The mode of transmission is autosomal dominant.
Pure mitochondrial myopathy (ORPHA:254854)
Pure mitochondrial myopathy is a rare mitochondrial disease characterized by exclusive skeletal muscle involvement, without clinical evidence of other organ involvement, manifesting with progressive limb weakness, proximal limb muscle atrophy, and eye muscle anomalies (e.g. ocular motility restriction, ptosis). Patients may present with lactic acidosis, diffuse myalgia and overall fatigability (particularly during/after physical activities), dysphagia, and diminished deep tendon reflexes.
Pustular pyoderma gangrenosum (ORPHA:538866)
A rare subtype of pyoderma gangrenosum characterized by multiple painful, sterile pustules with a surrounding erythematous halo, predominantly occurring on the trunk and extensor surfaces of the limbs, and potentially persisting for months. Histopathology shows a dermal neutrophilic infiltrate and subcorneal neutrophilic micropustules. The condition is commonly associated with inflammatory bowel disease.
Pustulosis palmaris et plantaris (ORPHA:163927)
A rare skin disease characterized by chronic eruption of sterile pustules on an erythematous and desquamative background. The lesions are usually painful and affect the palms and soles, sometimes also the lateral aspects of hands and feet. Nail lesions (such as nail pitting, onycholysis, subungual pustules, and nail dystrophy) are also observed. The condition takes a chronic and relapsing course. Typical associations are psoriatic arthritis, thyroid gland dysfunction, and smoking.
Pycnodysostosis (ORPHA:763)
Pycnodysostosis is a genetic lysosomal disease characterized by osteosclerosis of the skeleton, short stature and brittle bones.
Epidemiology
It is very rare, the exact prevalence is unknown but it is less than 1/100,000.
Clinical description
The disease is discovered at variable ages, ranging from 9 months to 50 years. The condition is most often diagnosed in childhood, but sometimes the condition is not detected until adulthood, usually as a result of a fracture or a routine examination. The most frequent clinical or radiological manifestations of the disease are osteosclerosis, short stature or dwarfism, acroosteolysis of the distal phalanges, fragile bones associated with spontaneous fractures and dysplasia of the clavicles. Patients present with characteristic cranial malformations: a voluminous skull with wormian bones present and persistence of the anterior fontanelle, and a small mandible. Dental abnormalities such as decayed, poorly located or abnormally shaped (pointed or conical) teeth and delayed tooth eruption may be observed. Nails are sometimes irregular and cracked. Very rarely, the disease is associated with anemia, hepatosplenomegaly, hematologic alterations, respiratory distress and sleep apnea. The short stature is variable but moderate (1.35m to 1.50m).
Etiology
Pycnodysostosis is due to mutations in the gene encoding cathepsin K (localized to 1q21), a lysosomal enzyme secreted by osteoclasts, which allows the division of proteins of the bone matrix (collagen type I, osteonectin or osteopontin).
Diagnostic methods
Diagnosis is clinical and should be confirmed by radiographic examination of the entire skeleton and skull.
Differential diagnosis
Differential diagnoses include osteoporosis, osteopetrosis, cleidocranial dysplasia and idiopathic acroosteolysis (see these terms).
Genetic counseling
Inheritance is autosomal recessive.
Management and treatment
Management is symptomatic and multidisciplinary. It includes orthopedic monitoring, treatment of fractures, of which consolidation is sometimes slow, and static vertebral surveillance to detect frequent spondylolisthesis.
Prognosis
The prognosis is favorable; the disease is not progressive.

                            Last update: 
                            December 2008


                            - Expert reviewer(s): 
                            Dr Martine LE MERRER
PYCR2-related microcephaly-progressive leukoencephalopathy (ORPHA:481152)
PYCR2-related microcephaly-progressive leukoencephalopathy is a rare, genetic, syndromic intellectual disability disorder characterized by progressive postnatal microcephaly, cerebral hypomyelination and severe psychomotor developmental delayed with absent speech, as well as axial hypotonia, appendicular hypertonia with hyperextensibility of the wrists and ankles, hyperreflexia, severe muscle wasting and failure to thrive. Associated craniofacial dysmorphism includes triangular facies with bitemporal narrowing, down- or upslanting palpebral fissures, malar hypoplasia, large malformed ears with overfolded helices, upturned bulbous nose, long smooth philtrum and thin vermilion borders.
Pyknoachondrogenesis (ORPHA:3003)
A lethal skeletal osteochondrodysplasia characterized by severe generalized osteosclerosis.
Epidemiology
The disease is very rare and only five cases (four males and one female) have been reported in the literature so far.
Clinical description
Pyknoachondrogenesis may be detected prenatally due to the extreme shortening of the limbs and hydrops fetalis, or is recognized at birth. The main clinical manifestations include a large head, palpebral edema, a flat nose, low-set ears, a short neck, a short and wide trunk, a prominent abdomen, and severe micromelic dwarfism.
Etiology
Etiology remains unknown. Familial occurrence of affected sibs of both sexes points to an autosomal recessive pattern of inheritance but parental consanguinity has not been reported.
Diagnostic methods
Diagnosis is based on clinical findings and typical radiographic features. X-rays show marked sclerosis of the facial bones and extremities, and poor ossification elsewhere.
Differential diagnosis
Achondrogenesis (see this term) is the main differential diagnosis.
Antenatal diagnosis
Prenatal diagnosis of pyknoachondrogenesis may be made by ultrasound.
Prognosis
Pyknoachondrogenesis has a lethal outcome, either prenatally or during the early neonatal period.

                            Last update: 
                            November 2008
Pyramidal molars-abnormal upper lip syndrome (ORPHA:2561)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by a variable combination of dental, cutaneous, ocular, and bone abnormalities, including pyramidal and fused molar roots, taurodontism, an abnormal upper lip without a cupid's bow and thickened and wide philtrum, juvenile glaucoma, syndactyly, and clinodactyly. There have been no further descriptions in the literature since 1973.
Pyridoxal phosphate-responsive seizures (ORPHA:79096)
A very rare neonatal epileptic encephalopathy disorder characterized clinically by onset of severe seizures within hours of birth that are not responsive to anticonvulsants, but are responsive to treatment with pyridoxal phosphate.
Pyruvate carboxylase deficiency, benign type (ORPHA:353320)
Benign pyruvate carboxylase (PC) deficiency (Type C) is a rare, very mild form of PC deficiency characterized by episodic metabolic acidosis and normal or mildly delayed neurological development.
Epidemiology
Benign PC deficiency is a very rare form of PC deficiency and has been described in fewer than 10 patients to date. No ethnic predilection has been reported.
Clinical description
Onset typically occurs during the first year of life with episodic metabolic acidosis associated with lactic acidemia and occasionally with ketoacidosis during metabolic stress. Neurological development is normal or mildly impaired. Other signs include dystonia, episodic ataxia, dysarthria, transitory hemiparesis and seizures.
Etiology
Type C PC deficiency is caused by mutations in the PC gene (11q13.4-q13.5).
Diagnostic methods
Blood lactic acid levels are usually between 2 and 5 mmol/l. The abnormal biochemical parameters found in severe forms of PC deficiency are absent in patients with Type C, although lysine, proline and alanine may be elevated, while citrulline is normal. PC enzyme activity assay demonstrating deficiency of the PC enzyme in fibroblasts is also diagnostic, along with mutations in the PC gene identified via molecular genetic testing.
Genetic counseling
Pyruvate carboxylase deficiency is inherited in an autosomal recessive manner.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Darryl DE VIVO  - Dr Dong WANG
Pyruvate carboxylase deficiency, infantile type (ORPHA:353308)
Infantile pyruvate carboxylase (PC) deficiency (Type A) is a rare, severe form of PC deficiency characterized by infantile-onset, mild to moderate lactic acidemia, and a generally severe course.
Epidemiology
The specific prevalence of type A pyruvate carboxylase deficiency is not known but it has been reported most often in Native Americans from North American Algonquian-speaking groups including the Mi'kmaq, Cree, and Ojibwa tribes. In these groups, the carrier frequency may be as high as 1/10.
Clinical description
Patients with Type A PC deficiency usually first present with symptoms at the age of two to five months, often after normal early development. Clinical manifestations include mild to moderate metabolic acidosis with acute vomiting and tachypnea, failure to thrive, apathy, delayed intellectual and motor development, hypotonia, pyramidal dysfunction, ataxia, nystagmus and seizures. Renal tubular acidosis has also been reported.
Etiology
PC deficiency is caused by mutations in the PC gene (11q13.4-q13.5).
Diagnostic methods
Biochemical testing shows hypoglycemia and ketosis, increased alanine and proline levels, but normal citrulline and lysine levels, along with a normal lactate-to-pyruvate ratio despite acidemia, and normal hydroxybutyrate/acetoacetate (H/A) ratio in plasma. Blood lactic acid levels are usually between 2 and 10 mmol/l. PC enzyme activity assay demonstrating deficiency of the PC enzyme in fibroblasts is also diagnostic, along with mutations in the PC gene identified via molecular genetic testing.
Genetic counseling
PC deficiency is inherited in an autosomal recessive manner.
Prognosis
Most affected patients die in infancy or in early childhood. Surviving children require special care and schooling.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Darryl DE VIVO  - Dr Dong WANG
Pyruvate carboxylase deficiency, severe neonatal type (ORPHA:353314)
Severe neonatal pyruvate carboxylase (PC) deficiency (Type B) is a rare, extremely severe form of PC deficiency characterized by severe, early-onset metabolic acidosis, and a generally fatal outcome in early infancy.
Epidemiology
The exact prevalence of Type B pyruvate carboxylase deficiency is not known. The disorder has been reported to be more common in populations of Arab descent (Algerian, Egyptian, and Saudi Arabian). Higher incidence is also reported in France, Germany and the United Kingdom.
Clinical description
Patients develop clinical manifestations during the first 72 hours of life with severe truncal hypotonia and tachypnea. Subsequent clinical signs include anorexia, failure to thrive, hepatomegaly, myoclonic or generalized tonic-clonic seizures, stupor, pyramidal dysfunction, abnormal movements (high-amplitude tremor and dyskinesia), abnormal limb and ocular movements and severe impairment of mental and motor development. Renal tubular acidosis has been reported.
Etiology
PC deficiency is caused by mutations in the PC gene (11q13.4-q13.5).
Diagnostic methods
The biochemical hallmarks of Type B pyruvate carboxylase deficiency include elevated lactate/pyruvate (L/P) ratio, ketoacidosis with low hydroxybutyrate/acetoacetate (H/A) ratio in plasma, hypoglycemia, increased citrulline, proline, lysine and alanine levels, low glutamine, hyperammonemia and hypernatremia. Blood lactic acid levels are usually above 10 mmol/l. PC enzyme activity assay demonstrating deficiency of the PC enzyme in fibroblasts is also diagnostic, along with mutations in the PC gene identified via molecular genetic testing.
Genetic counseling
Pyruvate carboxylase deficiency is inherited in an autosomal recessive manner.
Prognosis
The prognosis is very poor with almost all affected infants dying within the first three months of life.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Darryl DE VIVO  - Dr Dong WANG
Pyruvate dehydrogenase E1-alpha deficiency (ORPHA:79243)
A disorder that is the most frequent form of pyruvate dehydrogenase deficiency (PDHD) characterized by variable lactic acidosis, impaired psychomotor development, hypotonia and neurological dysfunction.
Epidemiology
Prevalence is unknown. Over 200 patients have been reported and while there are approximately equal numbers of males and females, male patients are generally more severely affected.
Clinical description
Patients present with a range of classic signs and symptoms of PDHD, including lactic acidosis, poor feeding, lethargy, tachypnea, developmental delay, growth retardation, poor acquisition or loss of motor milestones, hypotonia, seizures, ataxia and dystonia. Structural brain lesions including cortical atrophy, dilated ventricles, and incomplete corpus callosum, absence of the medullary pyramids and ectopia of the olivary nuclei are commonly observed, especially in female patients heterozygous for the disease-causing mutations that result in complete deficiency of E1-alpha subunit protein in cells expressing the gene mutation.
Etiology
The disease is caused by deficiency of the E1-alpha subunit of the PDH complex related to mutations in the PDHA1 gene (Xp22.1).
Genetic counseling
The pattern of inheritance is X-linked.

                            Last update: 
                            April 2012


                            - Expert reviewer(s): 
                            Dr Garry BROWN
Pyruvate dehydrogenase E1-beta deficiency (ORPHA:255138)
Pyruvate dehydrogenase E1-beta deficiency is an extremely rare form of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by severe lactic acidosis, developmental delay and hypotonia.
Epidemiology
Prevalence is unknown. About 8 cases have been reported to date.
Clinical description
Patients presented with lactic acidosis and hypotonia at birth and were often from consanguineous families. There are no specific clinical features that distinguish this condition from pyruvate dehydrogenase E1-alpha deficiency.
Etiology
The disorder is caused by mutations in the gene coding for the E1-beta subunit of the PDH complex (PDHB; 3p21.1-p14.2).
Genetic counseling
The pattern of inheritance is autosomal recessive.

                            Last update: 
                            April 2012


                            - Expert reviewer(s): 
                            Dr Garry BROWN
Pyruvate dehydrogenase E2 deficiency (ORPHA:79244)
A very rare form of pyruvate dehydrogenase deficiency (PDHD) characterized by variable lactic acidosis and neurological dysfunction, mainly appearing during childhood.
Epidemiology
Prevalence is unknown. Only 4 cases have been reported to date.
Clinical description
Patients with E2 deficiency generally present later in childhood with movement disorders and lesions in the globus pallidus similar to those found in patients with pantothenate kinase-associated neurodegeneration (see this term). Other signs include general hypotonia and delayed psychomotor development. Lactate concentration may be normal in both blood and cerebrospinal fluid.
Etiology
The condition is caused by mutations in the DLATgene (11q23.1) encoding the dihydrolipoamide acetyl transferase E2 subunit of the PDH complex. Parental consanguinity is commonly reported.
Genetic counseling
The pattern of inheritance is autosomal recessive.

                            Last update: 
                            April 2012


                            - Expert reviewer(s): 
                            Dr Garry BROWN
Pyruvate dehydrogenase E3 deficiency (ORPHA:2394)
Pyruvate dehydrogenase E3 deficiency is a very rare subtype of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by either early-onset lactic acidosis and delayed development, later-onset neurological dysfunction or liver disease.
Epidemiology
Prevalence is unknown. About 20 cases have been reported to date.
Clinical description
The majority of patients have presented with neonatal lactic acidosis or with lactic acidosis, delayed development and hypotonia during infancy. A few patients have presented later in childhood with ataxia and dystonia with normal cognitive development. A separate group of patients, essentially all of Ashkenazi Jewish origin and many homozygous for a common G229C missense mutation, present with episodic vomiting, abdominal pain, encephalopathy and liver cell dysfunction. In some patients, there is evidence of branched chain alpha-ketoacid dehydrogenase deficiency, with elevated concentrations of the branched chain amino acids and their metabolites. However, clinical manifestations in most cases appear to be related to the pyruvate dehydrogenase deficiency.
Etiology
The disorder is caused by mutations in the DLD gene (7q31-q32).
Genetic counseling
The pattern of inheritance is autosomal recessive.

                            Last update: 
                            April 2012


                            - Expert reviewer(s): 
                            Dr Garry BROWN
Pyruvate dehydrogenase E3-binding protein deficiency (ORPHA:255182)
Pyruvate dehydrogenase E3-binding protein deficiency is a rare mild form of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by variable lactic acidosis and neurological dysfunction.
Epidemiology
Prevalence is unknown. About 20 cases have been reported to date. The disorder is more frequent than PDHD E2 deficiency but less frequent than E1-alpha deficiency (see these terms).
Clinical description
Patients usually present with neonatal lactic acidosis or with delayed development and hypotonia during infancy. In contrast to other forms of pyruvate dehydrogenase deficiency, patients with E3 binding protein deficiency often survive well into childhood or adult life as there is some assembly of the pyruvate dehydrogenase complex even with complete deficiency of this protein. Thinning or agenesis of the corpus callosum is a common finding on MRI imaging of the brain.
Etiology
PDHD E3 binding protein deficiency is caused by a mutation in the PDHX gene (11p13) encoding the E3 binding protein subunit; also known as component X of the pyruvate dehydrogenase complex.
Genetic counseling
The pattern of inheritance is autosomal recessive.

                            Last update: 
                            April 2012


                            - Expert reviewer(s): 
                            Dr Garry BROWN