CSP Exam Prep Course: Enzyme Disorders

Vocabulary practice flashcards covering genetic mutations, disease phenotypes, diagnostic markers, and specialized pharmacotherapies for enzyme and lysosomal storage disorders included in the CSP Exam Prep Course.

Fabry Disease

A rare X-linked lysosomal storage disorder caused by mutations in the GLA gene that result in a deficiency of the enzyme α-galactosidase A (AGAL-A) and toxic accumulation of globotriaosylceramide (GL-3/Gb3).

Acroparesthesias

Excruciating pain in the hands and feet triggered by exercise, fevers, and stress, commonly presenting as an early symptom of Type 1 Classic Fabry disease.

Angiokeratomas

Clusters of red to blue rash-like discolorations on the skin associated with Type 1 Classic Fabry disease.

Fabrazyme® (agalsidase beta)

The first enzyme replacement therapy (ERT) marketed for Fabry disease; administered IV at $1\,mg/kg$ every 2 weeks, with a black box warning for hypersensitivity reactions including anaphylaxis.

Elfabrio® (pegunigalsidase alfa-iwxj)

An enzyme replacement therapy for Fabry disease dosed IV at $1\,mg/kg$ every 2 weeks, demonstrated in the BALANCE Phase III trial to be non-inferior to agalsidase beta with lower rates of treatment-emergent adverse events and infusion-related reactions.

Galafold® (migalastat)

An oral pharmacologic chaperone for Fabry disease that binds, stabilizes, and enhances residual enzyme activity in patients with amenable missense mutations; dosed at $123\,mg$ orally once every other day on an empty stomach.

Gaucher Disease

An autosomal recessive lysosomal storage disorder caused by mutations in the GBA gene, resulting in a deficiency of glucocerebrosidase and accumulation of glucocerebroside in tissues.

Type 1 Gaucher Disease

The most common form of Gaucher disease; non-neuronopathic and characterized by hematologic and skeletal abnormalities (thrombocytopenia, anemia, hepatosplenomegaly, bone pain, and fractures) with a normal life expectancy.

Cerezyme® (imiglucerase)

An enzyme replacement therapy approved for symptomatic Type 1 Gaucher disease in patients $> 2$ years of age, administered IV at doses ranging from $2.5\,units/kg$ three times weekly to $60\,units/kg$ once every 2 weeks.

Cerdelga® (eliglustat)

An oral substrate reduction therapy (SRT) for adult patients with Type 1 Gaucher disease who are CYP2D6 extensive, intermediate, or poor metabolizers; carries warnings for ECG changes and potential cardiac arrhythmias.

Zavesca® (miglustat)

An oral substrate reduction therapy that competitively and reversibly inhibits glucosylceramide synthase; dosed at $100\,mg$ three times daily (can be taken between meals to reduce diarrhea).

Pompe Disease

An autosomal recessive lysosomal and glycogen storage disorder (GSD type II) caused by mutations in the GAA gene, leading to acid alpha-glucosidase (acid maltase) deficiency and toxic lysosomal glycogen accumulation.

Lumizyme® (alglucosidase alfa)

An enzyme replacement therapy approved for all ages of Pompe disease; administered IV at $20\,mg/kg$ once every 2 weeks with boxed warnings for hypersensitivity/anaphylaxis, immune-mediated reactions, and acute cardiorespiratory failure.

Nexviazyme® (avalglucosidase alfa-ngpt)

An ERT approved for late-onset Pompe disease (LOPD) in patients $> 1$ year of age; dosed at $20\,mg/kg$ IV every 2 weeks for patients $\ge 30\,kg$ and $40\,mg/kg$ IV every 2 weeks for patients $< 30\,kg$.

Pombiliti® (cipaglucosidase alfa-atga)

An IV enzyme replacement therapy ($20\,mg/kg$ every 2 weeks) approved in combination with oral miglustat (Opfolda®) for adults with late-onset Pompe disease weighing $\ge 40\,kg$ who have not improved on existing ERT.

Opfolda® (miglustat)

An oral enzyme stabilizer taken with an unsweetened beverage approximately 1 hour prior to Pombiliti® infusion in adult LOPD patients weighing $\ge 40\,kg$; carries a warning for embryo-fetal toxicity.

Krabbe Disease

A rare autosomal recessive lysosomal storage disorder caused by a deficiency of galactocerebrosidase, leading to myelin sheath destruction, nervous system lipid buildup, and characteristic spherical globoid cells.

Psychosine

A cytotoxic lipid biomarker used to evaluate Krabbe disease progression and monitor the efficacy of hematopoietic stem cell transplantation (HSCT), which should decrease following successful transplant.

Maple Syrup Urine Disease (MSUD)

An autosomal recessive disorder caused by a deficiency in branched-chain alpha-keto acid dehydrogenase, leading to the accumulation of branched-chain amino acids (leucine, isoleucine, valine) and toxic ketoacids, producing a distinct sweet odor.

Phenylketonuria (PKU)

An autosomal recessive inborn error of metabolism caused by mutations in the PAH gene, leading to deficiency of phenylalanine hydroxylase and the neurotoxic accumulation of phenylalanine.

Kuvan® (sapropterin dihydrochloride)

A phenylalanine hydroxylase activator indicated in combination with a phenylalanine-restricted diet for PKU patients $> 1$ month of age, administered orally once daily with food at $10\text{ to }20\,mg/kg$.

Palynziq® (pegvaliase-pqpz)

A PEGylated enzyme therapy indicated for adults with PKU who have blood phenylalanine levels $> 600\,\mu mol/L$; administered subcutaneously and carries a black box warning for anaphylaxis.

Metachromatic Leukodystrophy (MLD)

A rare genetic disorder caused by ARSA (or PSAP) mutations leading to arylsulfatase A deficiency, sulfatide accumulation, and progressive demyelination of both the central and peripheral nervous systems.

Lenmeldy™ (atidarsagene autotemcel)

A one-time autologous hematopoietic gene therapy delivering functional copies of the ARSA gene to treat pre- or minimally symptomatic early MLD following myeloablative conditioning with busulfan.

Xenpozyme® (olipudase alfa-rpcp)

An enzyme replacement therapy indicated for adult and pediatric non-CNS manifestations of acid sphingomyelinase deficiency (Niemann-Pick Disease Types A and B), dosed IV at $0.1\,mg/kg$ in adults and $0.03\,mg/kg$ in pediatrics.

Tay-Sachs Disease

An autosomal recessive neurodegenerative lysosomal storage disorder caused by hexosaminidase A deficiency, causing GM2 ganglioside accumulation in neurons and presenting with acoustic hypersensitivity and macular cherry-red spots.

Wilson’s Disease

An autosomal recessive disorder caused by ATP7B gene mutations that impair biliary copper excretion, causing toxic copper accumulation in the liver, brain, and other organs.

Kayser-Fleischer Ring

A golden-brown ring of copper deposition around the cornea of the eye, pathognomonic for Wilson’s disease.

Cuprimine® (penicillamine)

An oral copper chelator used to treat Wilson’s disease (maximum dose $2\,g/day$); requires dosage reduction by $25\text{--}50\%$ during pregnancy and carries a boxed warning regarding toxicity and physician experience.

Syprine® (trientine dihydrochloride)

An oral copper-chelating compound indicated for the treatment of patients with Wilson’s disease who are intolerant to penicillamine.

Cuvrior® (trientine tetrahydrochloride)

An oral copper chelator taken on an empty stomach in divided doses twice daily, approved for stable, de-coppered adult Wilson’s disease patients who are tolerant to penicillamine.

Galzin® (zinc acetate)

An oral agent dosed at $50\,mg$ three times daily ($25\text{--}50\,mg$ TID in pregnancy) that blocks copper absorption from the gastrointestinal tract in patients with Wilson's disease.

Leipzig Scoring System

A diagnostic and severity assessment scale for Wilson's disease; a score of 7 or higher indicates severe disease warranting urgent referral for liver transplantation.