Abstract: A child with lactic acidosis, severe mental and developmental retardation, and proximal renal tubular acidosis is presented. [typeset.io]

Three types of PC deficiency have been recognized, based on clinical presentation. [ncbi.nlm.nih.gov]

Subdivisions of Pyruvate Carboxylase Deficiency pyruvate carboxylase deficiency type A pyruvate carboxylase deficiency type B pyruvate carboxylase deficiency type C General Discussion Pyruvate carboxylase deficiency (PC deficiency) is a rare genetic disorder present [rarediseases.org]

Age of presentation for the most serious forms varies from the prenatal period to early infancy. Severe disease has prenatal onset with congenital brain abnormalities. [9] Type A cases manifest in early infancy. [emedicine.medscape.com]

• Developmental Delay

  Diagnosis PC deficiency is suspected in individuals with failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. PC deficiency is diagnosed by physical symptoms and laboratory studies. [rarediseases.org]

  Characteristic features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). [medlineplus.gov]

  Overview Overview Pyruvate carboxylase (PC) deficiency is a rare inborn error of metabolism that can cause developmental delay and failure to thrive starting in the neonatal or early infantile period. [emedicine.medscape.com]

  Older children may also have alopecia, ataxia, developmental delay, sensorineural hearing loss, optic atrophy, and recurrent infections. [ncbi.nlm.nih.gov]

• Weakness

  They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth. [medlineplus.gov]

  […] symptoms include developmental delay, intellectual disability, mixed acid-base disturbance with mild to moderate elevations in lactic acid and ketone bodies in the blood (lactic acidosis/ketoacidosis), abdominal pain, vomiting, tiredness and muscle weakness [rarediseases.org]

• Fatigue

  Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting). [medlineplus.gov]

• Vomiting

  Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting). [medlineplus.gov]

  […] infantile form) begins in infancy and symptoms include developmental delay, intellectual disability, mixed acid-base disturbance with mild to moderate elevations in lactic acid and ketone bodies in the blood (lactic acidosis/ketoacidosis), abdominal pain, vomiting [rarediseases.org]

  Metabolic acidosis caused by abnormal lactate production is associated with nonspecific symptoms such as moderate to severe lethargy, poor feeding, vomiting, and seizures, especially during periods of illness and metabolic stress. [emedicine.medscape.com]

  Episodes of acute vomiting, tachypnea, and acidosis are usually precipitated by metabolic or infectious stress. Most affected children die in infancy or early childhood, although some may survive to maturity. [ncbi.nlm.nih.gov]

• Failure to Thrive

  […] to thrive, developmental delay, recurrent seizures and a failure of the body to produce the necessary fuels for energy and neurotransmitters important for brain function. [rarediseases.org]

  Clinical features Failure to thrive Developmental delay Recurrent seizures Biochemical findings by PC deficiency type [Wang et al 2008] Type A. [ncbi.nlm.nih.gov]

  Overview Overview Pyruvate carboxylase (PC) deficiency is a rare inborn error of metabolism that can cause developmental delay and failure to thrive starting in the neonatal or early infantile period. [emedicine.medscape.com]

• Abdominal Pain

  Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting). [medlineplus.gov]

  pain, vomiting, tiredness and muscle weakness. [rarediseases.org]

• Ataxia

  II ataxia with lactic acidosis References Carbone MA, MacKay N, Ling M, Cole DE, Douglas C, Rigat B, Feigenbaum A, Clarke JT, Haworth JC, Greenberg CR, Seargeant L, Robinson BH. [medlineplus.gov]

  Synonyms of Pyruvate Carboxylase Deficiency ataxia with lactic acidosis, type II PC deficiency Subdivisions of Pyruvate Carboxylase Deficiency pyruvate carboxylase deficiency type A pyruvate carboxylase deficiency type B pyruvate carboxylase deficiency [rarediseases.org]

  Older children may also have alopecia, ataxia, developmental delay, sensorineural hearing loss, optic atrophy, and recurrent infections. [ncbi.nlm.nih.gov]

  Hypotonia, ataxia, tremors, and choreoathetosis are consistent with PC deficiency. Progressive motor pathway degeneration results in positive Babinski sign and spastic diplegia or quadriplegia. [emedicine.medscape.com]

• Seizure

  Diagnosis PC deficiency is suspected in individuals with failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. PC deficiency is diagnosed by physical symptoms and laboratory studies. [rarediseases.org]

  Clinical features Failure to thrive Developmental delay Recurrent seizures Biochemical findings by PC deficiency type [Wang et al 2008] Type A. [ncbi.nlm.nih.gov]

  They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth. [medlineplus.gov]

  Metabolic acidosis caused by abnormal lactate production is associated with nonspecific symptoms such as moderate to severe lethargy, poor feeding, vomiting, and seizures, especially during periods of illness and metabolic stress. [emedicine.medscape.com]

• Stupor

  Affected infants present with biochemical abnormalities, hypoglycemia, hyperammonemia, hypernatremia, anorexia, hepatomegaly, convulsions, stupor, hypotonia, pyramidal tract signs, abnormal movements (including high-amplitude tremor and dyskinesia), and [ncbi.nlm.nih.gov]

• Convulsions

  Type A (infantile form) is characterized by infantile onset with mild metabolic acidosis, delayed motor development, intellectual disability, failure to thrive, apathy, hypotonia, pyramidal tract signs, ataxia, nystagmus, and convulsions. [ncbi.nlm.nih.gov]

Treatment Treatments are aimed at stimulating the pyruvate dehydrogenase complex and providing alternative fuels. [emedicine.medscape.com]

An individual with PC deficiency was responsive to treatment with thiamine. [ncbi.nlm.nih.gov]

Standard Therapies Treatment of PC deficiency is aimed at providing alternative sources of energy for the body and alternative means of metabolizing pyruvate (anaplerotic therapy). [rarediseases.org]

Consultations Evaluation of the patient by an expert in metabolic and genetic disease is necessary to confirm the diagnosis, guide appropriate treatment, and determine prognosis. [emedicine.medscape.com]

[…] to the diagnosis): Blood, urine, and CSF measures of organic and amino acids; brain MRI and MRS analysis Evaluation by a pediatric neurologist skilled in metabolic and genetic disorders to confirm the diagnosis, guide the treatment, and determine the prognosis [ncbi.nlm.nih.gov]

Etiology The gene that encodes pyruvate carboxylase (PC) has been localized to chromosome band 11q13.2. PC deficiency is inherited from parents by an autosomal recessive inheritance pattern. [emedicine.medscape.com]

As of June 2022, The Human Gene Mutation Database (HGMD) listed 62 variants in the PC gene. [7] Epidemiology Pyruvate carboxylase (PC) deficiency is a rare disorder, with an estimated global incidence of 1 in 250,000 births. [7] Infantile-onset type A [emedicine.medscape.com]

Pathophysiology Pyruvate carboxylase (PC) deficiency affects metabolism in several major ways. [emedicine.medscape.com]

Pathophysiology. The glutamine-glutamate cycle in astrocytes requires a continuous supply of oxaloacetate provided by the reaction catalyzed by PC enzyme activity. Genotype-Phenotype Correlations Type A. [ncbi.nlm.nih.gov]

Provide a high-carbohydrate and high-protein diet with frequent feedings to help prevent dependence on gluconeogenesis. Prevention of Secondary Complications Individuals with PC deficiency are very brittle metabolically. [ncbi.nlm.nih.gov]

A high-carbohydrate, high-protein diet may help to maintain an anabolic state and prevent activation of gluconeogenesis. [15] Fasting should be avoided. [emedicine.medscape.com]