flok Health

Cycle 3

Web:

Contact:

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 04/30/2026

Clinical

Disease Class

Genetic diseases

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

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

Amino acid metabolism defect

Cofactor/vitamin deficiency or defect

Enzyme deficiency

Nutrient processing disorder

Protein misfolding

Urea cycle defect

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

· Other labs that can be routinely monitored in this population include nutritional labs (vitamin D, vitamin B12, pre-albumin), liver and kidney function (with complete metabolic panel aka CMP) to monitor transaminases, creatinine, blood urea nitrogen, and asses for metabolic acidosis with anion gap, coagulation panels to discern synthetic liver function, coagulopathy panels in hypercoagulable conditions, and complete blood counts (CBC) to evaluate pancytopenia. Serial imaging is also used to evaluate for a plethora of consequences including cirrhosis, strokes, and brain damage. Serial neuropsychological evaluations are used to assess the progression of development and diagnose/manage neuropsychological conditions.

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

Expanded access (Compassionate Use)

Regulatory Agency-Approved for Symptom Relief

· Medical nutrition therapy for ALL flok disorders- regulated as medical nutrition; Phenylketonuria: Sapropterin dihydrochloride, Pegvaliase, Sephience; 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

Regulatory Agency-Approved to Cure or Modify the Disease

· Liver or Kidney transplantation (modifies, does not cure)

Therapies in Development

Devices/medical equipment

Dietary & metabolic therapies (medical food, dietary restriction, supplements, etc.)

Gene therapy

Small molecule therapy (novel small molecule drugs)

Surgical & interventional

Therapeutic Development Stages

Approved/Available

Awaiting final regulatory decision

IND/CTA submitted but not approved

In clinical trials (Phase I, II, III, or IV)

In preclinical development

In research/exploratory phase

Therapeutic Development Role

Focus group participation or coordination

Recruitment and outreach to patients

Results dissemination (including publications)

Organizational & Research

Cell Lines

None

Cell Lines, share

N/A

Disease Model

None

Disease Model, share

N/A

Organizational Challenges

Barriers we encounter include: helping patients understand the value of getting engaged in research and managing the burden thereof; ensuring our organizational knowledge and that of community members is adequately appreciated/compensated in this process; understanding how best to structure collaborative research engagements so that they benefit the community and support the org while protecting the integrity of our work.

Clinical Trial Role

Focus group

Meeting with regulators

Recruitment and outreach, patients

Results dissemination, publication

Study material design, review (not protocol)

Clinical Trial Types

Observational

Phase 2

Phase 3

Biobank, Institution

None

Center of Excellence, Institution

None

Registry

Yes, we have a registry that we created

Data Collected, Registry

Genetic data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Patients

Platform, Registry

Other

Natural History Study

Yes, we have a natural history study that we created

Data Collected, Natural History Study

Genetic data

Medication usage

Patient-reported outcomes

Platform, Natural History Study

Other

FDA Patient Listening Session

FDA Patient-Focused Drug Development (PFDD) Program

Yes

ICD Codes

Yes, we have an ICD-10 code specific to our exact disease

Diagnostic Guidelines

Science Advisory Board Policies

No policies

Research Network Policies

Has CRN but no policies

Patient Priority Survey

Research Roadmap

We don't have a Research Roadmap

None

Europe

North America

None