flok Health
Cycle 3
Inherited disorders of protein metabolism, such as Classical Homocystinuria (HCU), Maple Syrup Urin e Disease (MSUD), Phenylketonuria (PKU), Tyrosinemia, Organic Acidemias, and Urea Cycle Disorders (UCDs).
Last updated 04/30/2025
Clinical
Disease Class
Inherited metabolic disorder
Body Systems
Cardiovascular / Circulatory
Digestive
Endocrine
Hematopoietic / Lymphatic / Immune
Integumentary / Exocrine
Metabolic
Muscular / Skeletal
Nervous / Sensory
Renal / Urinary / Excretory
Reproductive
Respiratory
Organs
Arteries
Bile ducts
Bladder
Blood
Bone marrow
Bones
Brain
Breasts
Connective tissue / joints
Esophagus
Eyes
Gallbladder
Hair
Heart
Intestines
Kidneys
Liver
Lungs
Mouth / teeth
Muscles
Nails
Nerves
Ovaries
Pancreas
Parathyroid
Pituitary glands
Skin
Spinal cord
Spleen
Stomach
Thyroid
Uterus
Veins
Known Genetic Link
Yes, one or more genes directly cause the condition
causative_genes
ARG1
ASL
ASS
BCKDHA
BCKDHB
CBS
CPSI
DBT
DNAJC12
FAH
GCH1
HPD
MMAA
MMAB
MMADHC
MMADHC
MMUT
MTHFR
MTR
MTRR
NAGS
OTC
PAH
PCBD1
PCCA
PCCB
PTS
QDPR
TAT
contributory_genes
None specified / unknown
Type of Inheritance
Autosomal recessive
X-linked recessive
Newborn Screening
Yes, for some genes
Disease Mechanism(s)
Abnormal protein degradation
Cofactor deficiency
Enzyme deficiency
Inherited metabolic disorder
Nutrient processing disorder
Pathogenic mutation
Protein misfolding
Age of Onset
Prebirth
Average Age at Diagnosis
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Elderly (age 65+)
Infancy (age 0-1)
Middle childhood (6-11)
Pre-Birth
Life Expectancy
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Elderly (age 65+)
Infancy (age 0-1)
Middle childhood (6-11)
Pre-Birth
Affected Sex(es)
Female
Intersex
Male
National Prevalence
10000+
Global Prevalence
10000+
National Incidence
51-100
Global Incidence
Unknown
Populations and/or ancestry with higher prevalence
Culturally- and geographically-influenced patterns – in Ireland, Turkey, and Norway, and U.S. Mennonite communities for example – lead to higher incidence of autosomal recessive conditions like those served by flok. There is very little published evidence on our conditions' incidence/prevalence rates, which vary widely for the six disorder groups (14 conditions) flok serves: Classical Homocystinuria, Maple Syrup Urine Disease, Organic Acidemias, Phenylketonuria, Tyrosinemia and Urea Cycle Disorders.
Symptoms / Phenotypes
abnormal brain features
abnormal consumption behavior
anxiety
behavioral changes
coma
kidney disease / nephropathy
liver disease
stroke
vision problems
Biomarkers
Diagnostic
· Serum phenylalanine, Serum homocysteine and serum methionine, Serum leucine, isoleucine and valine (BCAAs), Urine α-ketoisocaproic acid, α-keto-β-methylvaleric acid, and α-ketoisovaleric acid (ketoacid derivatives of BCAAs), Serum and urine methylmalonic acid, Serum and urine propionic acid, Serum 3-hydroxypropionate and carnitine esters, Serum ammonia, Serum citrulline, Serum arginosuccinate, Serum arginine, Urine orotic acid, Urine succinylacetone, Serum tyrosine
Monitoring
· Serum phenylalanine, Serum homocysteine and serum methionine, Serum leucine, isoleucine and valine (BCAAs), Serum and urine methylmalonic acid, Serum carnitine, Serum and urine propionic acid , Serum 3-hydroxypropionate and carnitine esters, Serum ammonia, Serum citrulline, Serum arginosuccinate, Serum arginine, Urine orotic acid, Urine succinylacetone, Serum tyrosine
Other
Prognostic
· Serum phenylalanine, Serum pheylalanine:serum tyrosine ratio, Urine phenylpyruvate and oxo-phenylacetate, Serum homocysteine and serum methionine, Serum cystathionine, Serum leucine, isoleucine and valine (BCAAs), Serum alloisoleucine, Urine α-ketoisocaproic acid, α-keto-β-methylvaleric acid, and α-ketoisovaleric acid (ketoacid derivatives of BCAAs), Serum and urine methylmalonic acid, Serum carnitine, Serum and urine propionic acid , Serum 3-hydroxypropionate and carnitine esters, Serum ammonia, Serum citrulline, Serum arginosuccinate, Serum arginine, Urine orotic acid, Urine succinylacetone, Urine delta-aminolevulinate, Serum tyrosine, Urine 4-hydroxyphenylpyruvate
Therapeutic
· Serum phenylalanine, Serum pheylalanine:serum tyrosine ratio, Urine phenylpyruvate and oxo-phenylacetate, Serum homocysteine and serum methionine, Serum leucine, isoleucine and valine (BCAAs), Serum alloisoleucine, Urine α-ketoisocaproic acid, α-keto-β-methylvaleric acid, and α-ketoisovaleric acid (ketoacid derivatives of BCAAs), Serum and urine methylmalonic acid, Serum carnitine, Serum and urine propionic acid , Serum 3-hydroxypropionate and carnitine esters, Serum ammonia, Serum citrulline, Serum arginine, Urine orotic acid, Urine succinylacetone, Urine delta-aminolevulinate, Serum tyrosine
Existing Therapies
Complementary and Alternative treatments
· Developmental therapies, as indicated
FDA-Approved for Symptom Relief
· Medical nutrition therapy for ALL flok disorders- regulated as medical nutrition; Phenylketonuria: Sapropterin dihydrochloride, Pegvaliase; Homocystinuria: pyridoxine, betaine anhydrous, folic acid, cobalamin, anticoagulation therapy, bisphosphonates; Urea cycle disorders: sodium phenylbutyrate, sodium benzoate, sodium phenylacetate, glycerolphenylbutyrate, carglumic acid, antihypertensives, nitric oxide, arginine, citrulline, antimicrobials, continuous renal replacement therapy, hemodialysis; Hereditary tyrosinemia type I: Nitisinone; Methylmalonic acidemia: cobalamin; Propionic acidemia: carnitine
FDA-Approved to Cure or Modify the Disease
· Liver or Kidney transplantation (modifies, does not cure)
Organizational & Research
Cell Lines
None
Cell Lines, share
N/A
Disease Model
None
Disease Model, share
N/A
Clinical Trial Role
Not involved
Biobank, Institution
None
Center of Excellence, Institution
None
Registry
No, we do not have a registry, but we plan to create one
Natural History Study
No, we do not have a natural history study, but we plan to create or collaborate on one
FDA Patient Listening Session
No
FDA Patient-Focused Drug Development (PFDD) Program
No
ICD Codes
Yes, we have an ICD-10 code specific to our exact disease
Diagnostic Guidelines
No
Science Advisory Board Policies
No policies
Research Network Policies
Has CRN but no policies
Research Roadmap
We don't have a Research Roadmap
International Chapters
None
International Partners
None