Case presentation
Case#: 64 year old (report), female
CaseHPOsFreeText: At age 52 years, sudden difficulty with swallowing and speech, ophthalmoparesis with a vertical and horizontal eye movement disorder, dysesthesia of the hands with a quality of “pins and needles” and a glove-like distribution, as well as generalized areflexia. Diagnosed with Miller Fisher syndrome. Treatment with intravenous immunoglobulins led to remission of symptoms. Abdominal pain since childhood. At 63 years of age, she had generalized epileptic seizures with prolonged postictal confusion, persisting diarrhea, abdominal pain, renal failure, repeat episodes of lactic acidosis. Ventilated for >8 weeks due to massive metabolic acidosis and respiratory failure during seizure; tracheotomy, PEG. VitB6 supplement. Rehabilitation, and recovered after several months.
CaseNotHPOsFreeText: Muscle strength was normal. Abdominal computer tomography (CT), magnetic resonance imaging (MRI) and gastroscopy were normal. No signs of infection in CSF. CT and MRI of the brain as well as abdominal- and thorax-CT were normal initially then fat embolies in brain, pulmonary embolism, vertebral fractures. EMG was normal. No signs of malnutrition or liver disease (which can cause hyperprolinemia).
CasePreviousTesting: No evidence of porphyria on “laboratory tests”, or diseases of copper metabolism, lead poisoning, or adrenoleukodystrophy. Muscle biopsy showed nonspecific atrophy, but no evidence of mitochondrial disease. Serum proline 3085 μmol/l (reference 90-342 μmol/l), urine proline 46,531 μmol/g Crea (reference < 100 μmol/g Crea), CSF proline 104 mg/dl (reference < 6 mg/dl), urine Hydroxyproline 1395 μmol/g Crea (reference <100). Vitamin-B6 was decreased at 3.3 μg/l (reference > 4.9 μg/l). “targeted genetic analyses by Sanger sequencing revealed no pathogenic variant within the PRODH-gene (hyperprolinemia type I)”
CaseMethod1: PCR
CaseMethod2: Sequencing
CaseGenotypingMethod: “targeted genetic analyses by Sanger sequencing” for ALDH4A1 (no further details).
Variant: Compound heterozygous, confirmed in trans (the patient’s son only has one of the variants) 1) NM_003748.3:c.62+1G>A, 2) NM_003748.3:c.349G>C (p.Asp117His)
ClinVar: 1) N/A; 2) N/A
CAID: 1) CA338769667; 2) CA338760898
gnomAD: 1) Not in gnomAD; 2) Not in gnomAD
VariantEvidence: No functional evidence for the missense change. Score: This patient is an adult with hyperprolinemia who is compound heterozygous for two variants in ALDH4A1, c.62+1G>A and c.349G>C (p.Asp117His). Neither variant is in gnomAD. Variants in PRODH have been ruled out.